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Chris Adams | McClatchy NewspapersApril 25, 2011

ALAMOGORDO, N.M. � During Lennie's life under the microscope,
science changed.

Starting in the 1960s, Lennie, a chimpanzee, was strapped in a spacesuit
for U.S. government test flights, and subjected to spinal taps. He was fed a
banana laced with triparanol, a drug already removed from the market for
humans. In the 1970s, he was a breeder, used to increase the supply of lab
chimps. In the 1980s and 1990s, he was infected with the HIV and hepatitis
viruses and subjected time and again to blood draws and biopsies.

In 2002, Lennie died at a federal primate facility in the New Mexico
desert, where many of his former cage-mates still live.

Today, those former cage-mates � about 180 of them � are at the center of
an impassioned debate between the National Institutes of Health and the
animal-rights community. The chimps at the Alamogordo Primate Facility have
been withheld from research the past 10 years as part of an agreement
between the NIH and the Air Force base where the facility is located. Now
the NIH wants to move the chimps away from Alamogordo, where they'll be
allowed to be put back into research. Animal-rights activists want them
retired to a grassy sanctuary.

Even before Lennie's death from apparent heart disease, though, science
was moving away from the kind of research that dominated much of his life.
Two years ago, a major drug-maker said it no longer would conduct research
on chimpanzees. Several countries have sworn off chimps as well.

Researchers say advances in laboratory techniques mean that knowledge
once gained only by examining a live animal now can be learned in a petri
dish. And an expanding body of evidence shows that chimps don't work as the
human fill-in that researchers once hoped they would.

The ethics of animal research also have evolved. What once was
commonplace is now controversial, and there's a growing feeling that chimps
should be spared the pain and mental anguish of research.

"For primate research, you had better be able to show me that you've got
something that's pretty promising: an HIV vaccine, a cancer drug," said
Arthur Caplan, a University of Pennsylvania ethicist who chaired a
government panel in the 1980s that set guidelines for animal research. "The
burden of justifying the research is on the researcher, and it's very high."

Some see it differently. Calling chimps crucial to advancing hepatitis C
research, the NIH wants to ship them from the facility in New Mexico to the
Texas Biomedical Research Institute in San Antonio. The director of the
Texas institute's primate facility called chimps "a wonderful model" for
certain research.

The use of chimps in research has been a hot-button issue for years. When
the NIH said last year that it planned to move the Alamogordo chimps back
into research, there was an outcry from advocates and some lawmakers; the
NIH announced in January that it will delay any move until an expert panel
of outsiders has reassessed its scientific rationale.

To understand the evolving science of chimp research, McClatchy talked
with researchers and animal-rights activists, reviewed the scientific
literature and read through thousands of pages of medical records that
recount the experimentation on and illnesses, behavior and deaths of Lennie
and his peers. In Defense of Animals, an advocacy group, obtained the
records after a five-year legal fight with the NIH. The group shared them
exclusively with McClatchy with no strings attached; McClatchy conducted its
own review of the records, which provide the most detailed look ever into
the day-to-day life of chimp experimentation.

Lennie, the one-time space chimp, was born about 1962 in Africa and was
brought to New Mexico, where he spent four decades in a range ofexperiments.

In 1970, he was given triparanol � it's not clear why � even after the
drug had been removed from the market after it was found to damage human
eyes. In the 1980s and 1990s, he participated in HIV/AIDS and hepatitis C
research.

Lennie's 540-page medical file and "Chimpanzee Resume" detail the regular
tests and blood draws, which required a "knockdown," an anesthetizing dart.
It was something Lennie resisted.

"Animal excited at knockdown," a 1998 record said."Excited knockdown," a
record in 1997 said. "Pyrexia"� fever � "possible due to excitement of
sedation," it read in1998 again.

His medical records show four spinal taps and one bone-marrow biopsy. He
was moved from cage to cage, often living alone, until 2001, when he moved
in with two younger males. Within a day, he was injured in a fight; his
weight dropped dramatically, partly because of his low standing among the
other males.

On Feb. 23, 2002, soon after eating his morning fruit, Lennie grabbed the
side of his cage with all four limbs and slowly collapsed to the floor.
Efforts to revive him failed.

In the mid-1980s, scientists who were working to understand HIV and the
disease it caused, AIDS, thought chimps would be a vital resource.

Eventually, at least 198 chimps were infected with HIV, according to
a1997 report by the National Research Council, a prestigious body affiliated
with the National Academy of Sciences. But just one developed and died from
an AIDS-like disease.

The council said chimps could still be of value. But in its report, it
concluded that "chimpanzees have not been a universally satisfactory model
for human diseases" and "HIV infection of chimpanzees has not been an ideal
model."

Before that assessment, the U.S. government had bred about 400 chimps.
The once-"critical model for understanding" HIV became "a surplus of
chimpanzees and a substantial management problem," the council report said.

Why didn't chimps work out as hoped?

Despite their similarity to humans, chimps don't react to infection the
same way. In HIV research, for example, a possible vaccine protected the
chimps but not people, NIH scientists wrote in the New England Journal of
Medicine in 2007. Also in 2007, an article in the British Medical Journal
concluded: "When it comes to testing HIV vaccines, only humans will do."

Jarrod Bailey, the science director for the chimp-release campaign of the
anti-animal testing New England Anti-Vivisection Society, pointed to one key
difference: HIV infection doesn't generally result in a significant decline
in T-cells � a type of disease-fighting white blood cell � in chimps; in
humans, it does. Bailey said that about 100 vaccines had been tested in
nonhuman primates, including chimpanzees, and success in animals didn't
translate to success in humans.

Earlier this year, Ajit Varki of the University of California-San Diego
and his colleagues reviewed chimp research, disease by disease, and found
that chimps and humans experienced disease differently. As they concluded in
The Annual Review of Pathology: "Humans appear to have several surprising
differences in the severity and/or incidence of diseases and pathologies
that cannot be explained by environmental factors."

It called into question chimps' usefulness as human stand-ins.

"Chimps and humans are extremely close genetically, so there is this
feeling that they should be a good model to study human diseases," Varki
said. "But most attention has been on what is similar. We should also pay
more attention to the differences."

Varki researches molecules known as "sialic acids." Fewer than70 genes
are known to be directly involved in sialic acid biology, and many of those
changed after humans and chimps shared a common ancestor. Because sialic
acids play a role in disease formation, that could partly explain why chimps
and humans react differently to disease, hesaid.

Even so, Varki doesn't think that chimps should be completely exempt from
research of the kind done on humans. His own research starts at places such
as the Yerkes National Primate Research Center in Atlanta, where
veterinarians doing annual physicals on animals are asked to take a little
extra blood. It's packed up and shipped on ice to Varki's lab in Southern
California to be tested and cultured.

"The technologies we use are getting more and more sophisticated," he
said. "We can use smaller samples. So we can do a lot more than we could 10
or 20 years ago."

Chimps now in federal labs could be used the same way, Varki said. Chimps
already infected with HIV or hepatitis, he said, could be monitored during
their annual exams. But Varki supports research only if it's no more
invasive to the chimps than it would be for a human test subject.

Animal rights groups say the failure of chimps in AIDS and other diseases
shows that it's time to abandon them as lab subjects.

"Why keep poking away at something that doesn't work?" asked John Pippin,
a doctor who works with the advocacy group Physicians Committee for
Responsible Medicine. "The NIH is struggling with are search model that is a
failure because they simply don't know what todo."

For its part, the NIH doesn't emphasize chimp use in HIV research.
Instead, it focuses on hepatitis. Chimps "proved invaluable in developing
the hepatitis A and B vaccines that are in use today," and they're the only
reliable animal to study the liver disease hepatitis C, the NIH said. The
chimps also could be used in drug testing, it said.

One example of the chimps' importance, the NIH said, can be found in an
article in the journal Science.

The research was conducted at the primate unit of the Texas Biomedical
Research Institute, which is scheduled to receive the Alamogordo chimps. The
study used an experimental drug to suppress hepatitis C virus in the liver;
the four chimps in the study underwent weekly blood draws or liver biopsies
for about six months. Researchers saw a decrease in the virus, and the
institute's chief scientific officer, John VandeBerg, said the study showed
"great promise."

But will it translate to humans?

In the journal Genome Biology, a reviewer said the results were "very
exciting" but cautioned that "results obtained in chimpanzees will not
necessarily extrapolate to humans. ... The chimpanzee is a very useful model
for HCV infection, but there are significant differences" in the way the
species experience hepatitis.

In fact, the drug already was being studied in humans before these chimp
results were in.

The chimp study began on April 29, 2008. A month later, drug maker
Santaris Pharma said it had begun a human safety trial with the drug. In
starting that trial, Santaris cited previous research in monkeys � not
chimps, a higher level of primate � and said, "We are excited now to be able
to evaluate the drug's efficacy and safety in human subjects."

If the drug already was being studied in humans, was the chimp experiment
even necessary? Bailey of the New England Anti-Vivisection Society said it
clearly wasn't: If the human trial showed the drug to be safe, the company
probably would have moved to the next stage of the process, no matter what
the chimp study showed. If it were unsafe in humans, it wouldn't progress.

"I would be extremely surprised to hear of any drug already in human
clinical trials that is looking effective, safe and showing real promise to
be terminated based on some experiments in chimpanzees," Bailey said.

The company disagrees, saying the chimp studies were necessary and that
they provided information vital to later steps in the drug development
process. If the chimp studies hadn't succeeded, Santaris spokesman Navjot
Rai said, the company "would not have moved forward" with more human
studies. He said regulators didn't require the company to use chimps, but
that the company itself considered them critical.

Nonetheless, the U.S. is increasingly out of step with the world.

Several countries have said they'd stop using chimpanzees in research.
That's one reason the NIH said "the United States maintains the only
chimpanzee resource worldwide" for hepatitis C research. Most countries
don't have such a resource because they stopped � or never started � chimp
testing.

GlaxoSmithKline, a drug maker that's involved in hepatitis C research,
said in 2008 that it would stop chimp research. While chimps had played an
important role for three decades, Glaxo said, "the case for using great apes
in the future is less clear than it may have been previously." New
scientific techniques had helped science move beyond the chimp, it added.

Beyond that, the ethics of chimpanzee research have evolved. In its
1997review, the National Research Council said using chimps was acceptable,
but it noted that chimps were different and couldn't be used like rats,
canines or even lesser primates.

"The similarity of chimpanzees to humans distinguishes them insubstantial
ways from other laboratory animals and implies a moral responsibility for
the long-term care of chimpanzees that are used for our benefit in
scientific research," it said. Given its connection from decades of watching
chimps on television or in zoos, the public "expects a high level of respect
for the animals," it added.

VandeBerg said his Texas institution did treat chimps differently.

"They are much closer to humans in every respect than monkeys are, in
physiology, immunology, cognitive ability," he said. "We accord chimpanzees
a special place among all the animals." They are used in experiments only if
no other animal will do, he said.

To animal-rights activists, the very act of the research � let alone
infecting chimps with viruses � is wrong. The simplest blood draw requires
them to be anesthetized by darts. Some animals � such as Lennie� react to
that with fear.

"I'm not a veterinarian, and I'm not involved in handling the animals,"
he added. "I certainly wouldn't even use the term knockdown. ... The chimp
is sedated or anesthetized. Certainly there's some stress." But, he added,
human patients experience stress as well. The complaints about regular
biopsies, he said, are overstated.